In an unusual move, the FDA posted a guidance document on its webpage describing how to handle tentative approvals titled “ANDA Submissions – Amendments and Requests for Final Approval to Tentatively Approved ANDAs” (here) prior to its announcement in the Federal Register with this accompanying note:

“We are posting this document on the FDA website as Federal Register (FR) publication is not currently available for this document.  This posting is to provide advance notice to the public.  When publication in the FR becomes available, this document will be available in the FR as will a notice detailing how to submit comments on this document.”

Obviously, this note has to do with the government shutdown, but the FDA felt its importance was significant to bypass the FR posting.

This document is extremely important and provides guidance that we may all have assumed but now is stated in no uncertain terms.  The advice:  make sure any requests for final approval or amendments to TA’ed ANDAs are submitted in sufficient time to ensure that the FDA has enough time to act on the submission before the first potential date of approval.

This means, if you are making changes to an ANDA that is in TA status that would require further FDA review prior to approval, you must submit the amendment in time for the FDA to complete its review.  Thus, if the amendment would fall under a ten-month review clock, then submit well in advance of the time required for the review and allow sufficient post-review time if the Agency finds deficiencies in your amendment.

The guidance document outlines advice from the FDA on ANDAs that have been in TA status for more than three years and those that have been in TA status for less than three years.  The FDA also alerts firms to review various label changes that may have been made to the reference listed drug product’s label since the TA was issued, as well as other changes (such as those in USP requirements or changes in bioequivalence recommendations) in determining when to amend the ANDA.  It is interesting to note that this is the first time I have seen the admonishment to review any changes in bioequivalence-specific guidance well in advance of when the ANDA might be able to be approved (termed the earliest lawful approval date throughout the document), suggesting that new recommendations will likely require new bioequivalence or in vitro testing.

Also, the document describes times when the FDA might delay assessment of an amendment, as described below:

“However, as described in the Amendments Guidance, FDA also may defer assessment of an amendment other than a request for final approval if the earliest lawful final approval date for that ANDA is not for several years.  For example, FDA may defer assessment of a labeling update to an ANDA with paragraph III certifications to patents that will not expire for several years.”

While it is important for the applicant to certify that an amendment requesting final approval contains no changes in the TA’ed application, be certain that no other unexpected changes (i.e., labeling or compendial changes or BE requirements) have occurred.  The request for final approval when no changes are made will receive a three-month goal date.  The take-home message:  allow yourself sufficient time in requesting final approval of an application that is in tentative approval status or in making changes post-issuance of the TA letter to ensure your application will be ready when the first lawful approval date arrives.  Don’t be left behind!